Co-development of human organoid-based new approach methodologies (nams)

Duration: 6-12 months

Methodology: Bullseye will co-develop an open-loop New Approach Methodology (NAM) combining human pluripotent stem cell (hPSC)-derived vascularized organoids, microfluidics, and AI to be used for drug efficacy and toxicity testing.

Organoid creation is established and will be provided by Bullseye. A commercial microfluidic platform validated by Bullseye will be provided with an option to co-develop a custom microfluidic system. Image-based datasets will be the primary read-out, with AI-assisted image analysis used to generate data sets.

Metrics: The microfluidic platform will maintain organoid viability for at least two weeks in culture, with an option to extend this time period. The microfluidic platform can be configured for both static and perfusion conditions. Viability will be assessed by image-based live/dead staining and contractility measurements. Options to perform gene expression, proteomic, and functional assays (e.g. single-cell transcriptomics, immunocytochemistry, flow cytometry, calcium imaging, and electrophysiology) are available.

Datasets: As described above.

Validation Plans: Simple organoid viability will be demonstrated at a minimum. If desired, established drugs known to be safe and effective or toxic and non-effective can be used to validate organoid responses compared to controls. If desired, new drug lead candidates can also be tested.

Next Steps: After completion, further drugs can be used to increase the NAM predictive power and/or a more complex NAM can be developed through another co-development program.